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Growth failure represents a so far untreatable undesired side-effect. As lithium chloride (LiCl) is known to induce cell renewal in various tissues, we hypothesized that LiCl may prevent glucocorticoid-induced growth failure.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We monitored growth of fetal rat metatarsals cultured ex-vivo with dexamethasone and\/or LiCl, while molecular mechanisms were explored through RNA sequencing by implementing the differential gene expression and gene set analysis. Quantification of \u03b2-catenin in human growth plate cartilage cultured with dexamethasone and\/or LiCl was added for verification.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>After 14 days of culture, the length of dexamethasone-treated fetal rat metatarsals increased by 1.4\u2009\u00b1\u20090.2\u2009mm compared to 2.4\u2009\u00b1\u20090.3\u2009mm in control bones (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). The combination of LiCl and dexamethasone led to bone length increase of 1.9\u2009\u00b1\u20090.3\u2009mm (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001 vs. dexamethasone alone). By adding lithium, genes for cell cycle and Wnt\/\u03b2-catenin, Hedgehog and Notch signaling, were upregulated compared to dexamethasone alone group.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>LiCl has the potential to partially rescue from dexamethasone-induced bone growth impairment in an ex vivo model. Transcriptomics identified cell renewal and proliferation as candidates for the underlying mechanisms. Our observations may open up the development of a new treatment strategy for bone growth disorders.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Impact<\/jats:title>\n                <jats:p><jats:list list-type=\"bullet\">\n                  <jats:list-item>\n                    <jats:p>LiCl is capable to prevent glucocorticoid-induced growth failure in rat metatarsals in vitro.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>The accompanying drug-induced transcriptomic changes suggested cell renewal and proliferation as candidate underlying mechanisms.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>Wnt\/beta-catenin pathway could be one of those novel mechanisms.<\/jats:p>\n                  <\/jats:list-item>\n                <\/jats:list><\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/s41390-024-03192-6","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T17:01:59Z","timestamp":1714410119000},"page":"952-963","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lithium rescues cultured rat metatarsals from dexamethasone-induced growth failure"],"prefix":"10.1038","volume":"96","author":[{"given":"Ondrej","family":"Soucek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ondrej","family":"Cinek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilly","family":"Velentza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerij","family":"Semjonov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Bezdicka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farasat","family":"Zaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"S\u00e4vendahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,29]]},"reference":[{"key":"3192_CR1","doi-asserted-by":"publisher","first-page":"2549","DOI":"10.1007\/s00431-022-04455-2","volume":"181","author":"S Ciancia","year":"2022","unstructured":"Ciancia, S. et al. 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